Project Area: Structure-function analysis and cell-signaling of metastasis-promoting multi-functional protease inhibitors
Proteases and their natural inhibitors control virtually all processes of life by controlling and remodeling the proteins in the microenvironment of any cell, its receptors, as well as growth factors. Imbalance of proteases and protease inhibitors promotes detrimental inflammatory processes during infections, tumor growth, and cancer metastasis.
We study the non-canonical function of Tissue-inhibitors of metalloproteinases (TIMPs), namely their newly-discovered potential to act, unexpectedly, as a cell signaling-inducing cytokine, which triggers pro-inflammatory function in immune cells as well as other organ-resident cells. We have identified the multi-functionality of TIMP-1 and could thereby explain the paradox that TIMP-1 correlates with bad prognosis of many diseases, although its canonical anti-proteolytic activity had led to the prediction that TIMP-1 should inhibit them. We employ a wide spectrum of technologies encompassing all aspects of molecular cloning/genetic
engineering, expression-vector design, biochemistry, cell culture including functional cell-assays, metabolic assays, protein-design and purification, flow-cytometry, histology, in silico-modeling, TIMSTOF, statistical analyses etc. in order to explore new structure-function relationships between TIMPs and their receptors, which we also identify in the process.
Through cooperation with colleagues in the clinic we constantly validate our data with material from the clinic towards a transfer of new knowledge from bench to the bedside.
If you have an M.Sc. in biochemistry, (molecular) biology, molecular biotechnology or similar, and would like to work towards a PhD or Dr. rer. nat., we are happy to welcome you in our group.
Please contact me at: achim.krueger[ät]tum.de